931 research outputs found

    Helicopter tail rotor thrust and main rotor wake coupling in crosswind flight

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    The tail rotor of a helicopter with a single main rotor configuration can experience a significant reduction in thrust when the aircraft operates in crosswind flight. Brown’s vorticity transport model has been used to simulate a main rotor and tail rotor system translating at a sideslip angle that causes the tail rotor to interact with the main rotor tip vortices as they propagate downstream at the lateral extremities of the wake. The tail rotor is shown to exhibit a distinct directionally dependent mode during which tail rotors that are configured so that the blades travel forward at the top of the disk develop less thrust than tail rotors with the reverse sense of rotation. The range of flight speeds over which this mode exists is shown to vary considerably with the vertical location of the tail rotor. At low flight speeds, the directionally dependent mode occurs because the tail rotor is immersed within not only the downwash from the main rotor but also the rotational flow associated with clusters of largely disorganized vorticity within the main rotor wake. At higher flight speeds, however, the tail rotor is immersed within a coherent supervortex that strongly influences the velocity field surrounding the tail rotor

    Temperature Modulates Coccolithophorid Sensitivity of Growth, Photosynthesis and Calcification to Increasing Seawater pCO2

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    Increasing atmospheric CO2 concentrations are expected to impact pelagic ecosystem functioning in the near future by driving ocean warming and acidification. While numerous studies have investigated impacts of rising temperature and seawater acidification on planktonic organisms separately, little is presently known on their combined effects. To test for possible synergistic effects we exposed two coccolithophore species, Emiliania huxleyi and Gephyrocapsa oceanica, to a CO2 gradient ranging from ,0.5–250 mmol kg21 (i.e. ,20–6000 matm pCO2) at three different temperatures (i.e. 10, 15, 20uC for E. huxleyi and 15, 20, 25uC for G. oceanica). Both species showed CO2-dependent optimum-curve responses for growth, photosynthesis and calcification rates at all temperatures. Increased temperature generally enhanced growth and production rates and modified sensitivities of metabolic processes to increasing CO2. CO2 optimum concentrations for growth, calcification, and organic carbon fixation rates were only marginally influenced from low to intermediate temperatures. However, there was a clear optimum shift towards higher CO2 concentrations from intermediate to high temperatures in both species. Our results demonstrate that the CO2 concentration where optimum growth, calcification and carbon fixation rates occur is modulated by temperature. Thus, the response of a coccolithophore strain to ocean acidification at a given temperature can be negative, neutral or positive depending on that strain’s temperature optimum. This emphasizes that the cellular responses of coccolithophores to ocean acidification can only be judged accurately when interpreted in the proper eco-physiological context of a given strain or species. Addressing the synergistic effects of changing carbonate chemistry and temperature is an essential step when assessing the success of coccolithophores in the future ocean

    Surgeons’ perspectives on artificial intelligence to support clinical decision-making in trauma and emergency contexts: results from an international survey

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    Background: Artificial intelligence (AI) is gaining traction in medicine and surgery. AI-based applications can offer tools to examine high-volume data to inform predictive analytics that supports complex decision-making processes. Time-sensitive trauma and emergency contexts are often challenging. The study aims to investigate trauma and emergency surgeons’ knowledge and perception of using AI-based tools in clinical decision-making processes. Methods: An online survey grounded on literature regarding AI-enabled surgical decision-making aids was created by a multidisciplinary committee and endorsed by the World Society of Emergency Surgery (WSES). The survey was advertised to 917 WSES members through the society’s website and Twitter profile. Results: 650 surgeons from 71 countries in five continents participated in the survey. Results depict the presence of technology enthusiasts and skeptics and surgeons’ preference toward more classical decision-making aids like clinical guidelines, traditional training, and the support of their multidisciplinary colleagues. A lack of knowledge about several AI-related aspects emerges and is associated with mistrust. Discussion: The trauma and emergency surgical community is divided into those who firmly believe in the potential of AI and those who do not understand or trust AI-enabled surgical decision-making aids. Academic societies and surgical training programs should promote a foundational, working knowledge of clinical AI

    Chaperones rescue the energetic landscape of mutant CFTR at single molecule and in cell

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    Molecular chaperones are pivotal in folding and degradation of the cellular proteome but their impact on the conformational dynamics of near-native membrane proteins with disease relevance remains unknown. Here we report the effect of chaperone activity on the functional conformation of the temperature-sensitive mutant cystic fibrosis channel (Delta F508-CFTR) at the plasma membrane and after reconstitution into phospholipid bilayer. Thermally induced unfolding at 37 degrees C and concomitant functional inactivation of Delta F508-CFTR are partially suppressed by constitutive activity of Hsc70 and Hsp90 chaperone/co-chaperone at the plasma membrane and post-endoplasmic reticulum compartments in vivo, and at singlemolecule level in vitro, indicated by kinetic and thermodynamic remodeling of the mutant gating energetics toward its wild-type counterpart. Thus, molecular chaperones can contribute to functional maintenance of Delta F508-CFTR by reshaping the conformational energetics of its final fold, a mechanism with implication in the regulation of metastable ABC transporters and other plasma membrane proteins activity in health and diseases

    From seeing the writing on the wall, to getting together for a bowl: direct and compensating effects of Facebook use on offline associational membership

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    Research concerned with a decline of associational involvement has examined whether the use of social networking sites, such as Facebook, may reinvigorate or crowd out involvement in civil society. Yet, previous studies have not systematically investigated possible effects of Facebook use on associational membership. We posit that the effects of Facebook use are twofold: Facebook stimulates associational membership directly through its inherent networking features and indirectly by compensating for the lack of traditional mobilizing factors, such as social trust and internal efficacy. Relying on a probabilistic sample of German participants aged 18-49, our findings show that Facebook users are more likely to be members of voluntary associations and that Facebook use increases the likelihood of associational membership even for individuals with low levels of social trust and internal efficacy. Instead of crowding out offline associational involvement, Facebook use stimulates membership in voluntary associations, thus contributing to the vitality of civil society

    A comparison of flare forecasting methods, I: results from the “All-clear” workshop

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    YesSolar flares produce radiation which can have an almost immediate effect on the near-Earth environ- ment, making it crucial to forecast flares in order to mitigate their negative effects. The number of published approaches to flare forecasting using photospheric magnetic field observations has prolifer- ated, with varying claims about how well each works. Because of the different analysis techniques and data sets used, it is essentially impossible to compare the results from the literature. This problem is exacerbated by the low event rates of large solar flares. The challenges of forecasting rare events have long been recognized in the meteorology community, but have yet to be fully acknowledged by the space weather community. During the interagency workshop on “all clear” forecasts held in Boulder, CO in 2009, the performance of a number of existing algorithms was compared on common data sets, specifically line-of-sight magnetic field and continuum intensity images from MDI, with consistent definitions of what constitutes an event. We demonstrate the importance of making such systematic comparisons, and of using standard verification statistics to determine what constitutes a good prediction scheme. When a comparison was made in this fashion, no one method clearly outperformed all others, which may in part be due to the strong correlations among the parameters used by different methods to characterize an active region. For M-class flares and above, the set of methods tends towards a weakly positive skill score (as measured with several distinct metrics), with no participating method proving substantially better than climatological forecasts.This work is the outcome of many collaborative and cooperative efforts. The 2009 “Forecasting the All-Clear” Workshop in Boulder, CO was sponsored by NASA/Johnson Space Flight Center’s Space Radiation Analysis Group, the National Center for Atmospheric Research, and the NOAA/Space Weather Prediction Center, with additional travel support for participating scientists from NASA LWS TRT NNH09CE72C to NWRA. The authors thank the participants of that workshop, in particular Drs. Neal Zapp, Dan Fry, Doug Biesecker, for the informative discussions during those three crazy days, and NCAR’s Susan Baltuch and NWRA’s Janet Biggs for organizational prowess. Workshop preparation and analysis support was provided for GB, KDL by NASA LWS TRT NNH09CE72C, and NASA Heliophysics GI NNH12CG10C. PAH and DSB received funding from the European Space Agency PRODEX Programme, while DSB and MKG also received funding from the European Union’s Horizon 2020 research and in- novation programme under grant agreement No. 640216 (FLARECAST project). MKG also acknowledges research performed under the A-EFFort project and subsequent service implementation, supported under ESA Contract number 4000111994/14/D/MPR. YY was supported by the National Science Foundation under grants ATM 09-36665, ATM 07-16950, ATM-0745744 and by NASA under grants NNX0-7AH78G, NNXO-8AQ90G. YY owes his deepest gratitude to his advisers Prof. Frank Y. Shih, Prof. Haimin Wang and Prof. Ju Jing for long discussions, for reading previous drafts of his work and providing many valuable comments that improved the presentation and contents of this work. JMA was supported by NSF Career Grant AGS-1255024 and by a NMSU Vice President for Research Interdisciplinary Research Grant

    Ki-67 expression is superior to mitotic count and novel proliferation markers PHH3, MCM4 and mitosin as a prognostic factor in thick cutaneous melanoma

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    <p>Abstract</p> <p>Background</p> <p>Tumor cell proliferation is a predictor of survival in cutaneous melanoma. The aim of the present study was to evaluate the prognostic impact of mitotic count, Ki-67 expression and novel proliferation markers phosphohistone H3 (PHH3), minichromosome maintenance protein 4 (MCM4) and mitosin, and to compare the results with histopathological variables.</p> <p>Methods</p> <p>202 consecutive cases of nodular cutaneous melanoma were initially included. Mitotic count (mitosis per mm<sup>2</sup>) was assessed on H&E sections, and Ki-67 expression was estimated by immunohistochemistry on standard sections. PHH3, MCM4 and mitosin were examined by staining of tissue microarrays (TMA) sections.</p> <p>Results</p> <p>Increased mitotic count and elevated Ki-67 expression were strongly associated with increased tumor thickness, presence of ulceration and tumor necrosis. Furthermore, high mitotic count and elevated Ki-67 expression were also associated with Clark's level of invasion and presence of vascular invasion. High expression of PHH3 and MCM4 was correlated with high mitotic count, elevated Ki-67 expression and tumor ulceration, and increased PHH3 frequencies were associated with tumor thickness and presence of tumor necrosis. Univariate analyses showed a worse outcome in cases with elevated Ki-67 expression and high mitotic count, whereas PHH3, MCM4 and mitosin were not significant. Tumor cell proliferation by Ki-67 had significant prognostic impact by multivariate analysis.</p> <p>Conclusions</p> <p>Ki-67 was a stronger and more robust prognostic indicator than mitotic count in this series of nodular melanoma. PHH3, MCM4 and mitosin did not predict patient survival.</p

    Integrated analysis of DNA methylation and gene expression reveals specific signaling pathways associated with platinum resistance in ovarian cancer

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    <p>Abstract</p> <p>Background</p> <p>Cisplatin and carboplatin are the primary first-line therapies for the treatment of ovarian cancer. However, resistance to these platinum-based drugs occurs in the large majority of initially responsive tumors, resulting in fully chemoresistant, fatal disease. Although the precise mechanism(s) underlying the development of platinum resistance in late-stage ovarian cancer patients currently remains unknown, CpG-island (CGI) methylation, a phenomenon strongly associated with aberrant gene silencing and ovarian tumorigenesis, may contribute to this devastating condition.</p> <p>Methods</p> <p>To model the onset of drug resistance, and investigate DNA methylation and gene expression alterations associated with platinum resistance, we treated clonally derived, drug-sensitive A2780 epithelial ovarian cancer cells with increasing concentrations of cisplatin. After several cycles of drug selection, the isogenic drug-sensitive and -resistant pairs were subjected to global CGI methylation and mRNA expression microarray analyses. To identify chemoresistance-associated, biological pathways likely impacted by DNA methylation, promoter CGI methylation and mRNA expression profiles were integrated and subjected to pathway enrichment analysis.</p> <p>Results</p> <p>Promoter CGI methylation revealed a positive association (Spearman correlation of 0.99) between the total number of hypermethylated CGIs and GI<sub>50 </sub>values (<it>i.e</it>., increased drug resistance) following successive cisplatin treatment cycles. In accord with that result, chemoresistance was reversible by DNA methylation inhibitors. Pathway enrichment analysis revealed hypermethylation-mediated repression of cell adhesion and tight junction pathways and hypomethylation-mediated activation of the cell growth-promoting pathways PI3K/Akt, TGF-beta, and cell cycle progression, which may contribute to the onset of chemoresistance in ovarian cancer cells.</p> <p>Conclusion</p> <p>Selective epigenetic disruption of distinct biological pathways was observed during development of platinum resistance in ovarian cancer. Integrated analysis of DNA methylation and gene expression may allow for the identification of new therapeutic targets and/or biomarkers prognostic of disease response. Finally, our results suggest that epigenetic therapies may facilitate the prevention or reversal of transcriptional repression responsible for chemoresistance and the restoration of sensitivity to platinum-based chemotherapeutics.</p

    Support for Anonymous as Vicarious Dissent: Testing the Social Banditry Framework

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    This research uses the social banditry framework to propose that voiceless individuals in an unjust context may express their grievances vicariously. Specifically, it holds that individuals who perceive the system as unjust but lack political efficacy, express their anger against the system as support for actors whose behavior disrupts the system’s functioning. These actors are situated outside conventional societal and political structures of power, and institutions. To test the social banditry framework, two studies investigate attitudes toward Anonymous, a group of hackers who challenge the status quo using online tactics such as trolling. Study 1 (N = 304) demonstrates that appraising the system as more unjust, and perceiving lower political efficacy are positively linked to anger against the system, which in turn predicts more positive attitudes toward Anonymous. In contrast, stronger injustice-fueled anger and stronger political efficacy predict intentions to engage in direct forms of political action, such as protesting or voting. Study 2 (N = 410) replicates these findings, and theorizes and tests the role of individualistic and collectivistic values in predicting vicarious and direct expressions of dissent. Study 2 demonstrates that endorsement of horizontal individualism predicts positive attitudes towards Anonymous, whereas horizontal collectivism predicts engagement in direct political action. Implications and directions for future research are discussed
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